»
Glucose Control

The introduction of highly active antiretroviral therapy (HAART) has significantly improved the survival and quality of life of HIV-infected individuals. However, HARRT-regimen, especially those including PIs have also resulted in increased incidence of metabolic syndrome and diabetes. Eleven PIs are now available in US and at least eight of them are clearly associated with disturbance in glucose homeostasis. It is estimated that up to 40 of patients receiving Pi-based regimen show glucose...

The goals of therapy in GDM are to decrease both maternal and fetal morbidity and mortality attributed to the disease. In particular, to limit macrosomia, intrauterine demise and neonatal morbidity. Preventing macrosomia has been found to decrease birth trauma, and cesarean-section rate (51). Maternal hyperglycemia conclusively poses a threat to the well-being of the fetus. Fasting hyperglycemia (FPG &gt 105 mg dL) is associated with increased risk of fetal death (17,18). Higher postprandial...

The aldose reductase pathway has been extensively studied because of the presence of the enzyme in the retina, kidney, and nerves. These are all targets for the long-term complications and would present a unified model for the damage caused by chronic hyperglycemia. The enzyme increases its activity in the presence of high blood glucose levels and causes increased levels of sorbitol. Sorbitol dehydrogenase metabolizes the sorbitol that is then postulated to lead to other metabolic changes that...

Diabetes mellitus (DM) has emerged as one of the most common diseases of this century. Its incidence is on the rise and the numbers are projected to reach a dreaded level by the year 2030 (1). In the United States alone, 4000 cases of diabetes are diagnosed every day (2). Most of them are type 2 diabetes mellitus (T2DM), and overall 8 of the population carries this diagnosis (3). Hyperglycemia is the sine qua non for diabetes. It results from the disturbance of normal glucose homeostasis. Under...

Several large studies were published on prevention of diabetes type 2 by exercise combined with other interventions such as weight loss and intensified medical treatment. In one study 3234 nondiabetic patients with impaired glucose tolerance were randomly assigned to either placebo, metformin (850 mg twice daily), and lifestyle-modification program with the goals of a minimum of 7 weight loss and 150 min physical activity per week (52). Physical activity was only recommended, not supervised...

There is little published information about the clinical impact of hypoglycemia in type 2 diabetes. While it is reasonable to extrapolate from the experience in type 1 diabetes, there are obvious differences. As noted earlier, episodes of hypoglycemia become familiar events early in the course of type 1 diabetes. They are infrequent early in the course of type 2 diabetes, even during treatment with insulin secretagogues or insulin, but become progressively more frequent as the patient...

Hu et al. (39) published results from the Nurses' Heath Study including 84,941 female nurses followed from 1980 to 1996, and who were free of diagnosed cardiovascular disease and diabetes at baseline. During the 16 years follow-up 3300 new cases of type 2 diabetes were diagnosed. As shown in Figure 4 obesity was the single most important predictor of diabetes. Women whose body mass index was at least 35.0 km m2 had almost 40-fold risk of becoming diabetic compared to women whose body mass index...

Recent experimental studies suggest a multifactorial pathogenesis of diabetic neuropathy. Most data have been generated in the diabetic rat model, on the basis of which two approaches have been chosen to contribute to the clarification of the pathogenesis of diabetic neuropathy. Firstly, it has been attempted to characterize the pathophysiological, pathobiochemical, and structural abnormalities that result in experimental diabetic neuropathy. Secondly, specific therapeutic interventions have...

The incretin effect is absent or diminished in type 2 diabetes. GLP-1 still stimulates insulin secretion in type 2 diabetic patients at higher plasma concentrations, whereas GIP has lost most of its insulinotropic activity (27-29). The reason for the loss of the insulinotropic action of GIP has not completely been elucidated yet. Specific defects in GIP signaling and general secretory defects of the beta cell are most likely responsible. GLP-1 secretion as well as GLP-1 action is diminished in...

Institute of Clinical Diabetes Research, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University, DUsseldorf, Germany CLASSIFICATION, EPIDEMIOLOGY, AND CLINICAL IMPACT OF DIABETIC NEUROPATHY Diabetic neuropathy has been defined as a demonstrable disorder, either clinically evident or subclinical, that occurs in the setting of diabetes mellitus without other causes for peripheral neuropathy. It includes manifestations in the somatic and or autonomic parts of the...

Although many effective treatment modalities are available for the control of diabetes, glycemic control is still below national guidelines. Suboptimal treatment of diabetes in ethnic groups may be due to barriers that hinder effective treatment. The barriers at the level of the patient include poor diabetes-specific knowledge, lack of self-management skills and non-adherence to lifestyle modification such as diet and exercise. Others include, negative belief and attitudes about diabetes, low...

Efficacy, side effects, and compliance strongly depend on rational indications, education of patients on how to use the drug, and good dietary advice. Even with good clinical practice, a considerable variation in response and side effects is seen. Side effects depend, among other things, on the dose and time intervals for titration of optimal therapeutic dosage. It is essential to start with low doses of 25 mg of acarbose or miglitol twice a day, with a stepwise increase in 2 to 3 week...

A surgical procedure cannot be considered successful unless the patient recovers with an equal or improved quality of life and long-term survival. Patients with long standing diabetes are at increased risk for developing complications. The goal of preoperative assessment is to identify patient risk factors and quantify risk, in order to decide the appropriateness of the planned surgical procedure and the timing of surgery. History, physical, and selective tests are used to identify the presence...

Furthermore, while it is evident that both classes of drugs inhibiting the RAS appear to be beneficial, an important question remains is one class superior for the prevention of the development of cardiovascular and renal disease This particular issue has now been addressed by the DETAIL trial (66). DETAIL was a much-needed, long-term study comparing an ACE-inhibitor with an ARB head-to-head in a diabetic population. The 5-year, prospective, multicenter, double-blind study directly compared the...

MODY2 presents with mild, dietary manageable hyperglycemia and in the case of a positive family anamnesis, this MODY form is especially seen in children with the highest prevalence. Usually affected subjects are free of symptoms at diagnosis and are identified in routine health examinations Table 2 . Approximately half of the female mutation carriers present for the first time with gestation diabetes. The molecular causes of MODY2 are mutations in the glucokinase GCK gene and more than 200...

This was suggested in a report from the BARI trial, which evaluated patients with and without diabetes who had undergone revascularization with CABG or PTCA within three months after study entry 25 . Among the patients with diabetes, CABG significantly reduced the mortality after a subsequent MI relative risk 0.09 compared to angioplasty . BARI trial data and results from three other trials that reported results for patients with diabetes EAST, CABRI, and RITA were...

It has long been recognized that antidiabetic drugs can promote weight gain in subjects with type 2 diabetes. The strongest weight-promoting effect is exerted by insulin. In the diabetes control and complications trial DCCT , intensified insulin treatment was associated with substantial weight gain that resulted in unfavorable changes of lipid levels and blood pressure similar to those seen in the insulin resistance syndrome 24 . In the UKPDS, insulin treatment caused a mean weight gain of...

Diabetes mellitus DM refers to a number of disorders that share the common feature of elevated blood glucose levels. The classification accepted by the World Health Organization WHO 1,2 and the American Diabetes Association ADA 3,4 combines both clinical stages of hyperglycemia and the etiological types. Two main subtypes of diabetes are type 1, either autoimmune or idiopathic, and type 2, attributable to insulinresistance, insulin secretion defects, or both. Although diabetes has been known...

Given the predicted increase in the prevalence of diabetes worldwide and the progressive Westernization of lifestyles in developing countries, cardiovascular disease, which is increased two to five times in people with diabetes, has and will continue to have major implications for health and healthcare provision. Although the development of atherosclerosis and clinical vascular disease is multifactorial, dyslipidemia is a major contributing risk factor. Dyslipidemia is common in patients with...

Psychological stress has significant effects on the metabolism on individuals without diabetes by increasing counterregulatory hormones, which could result in elevated blood sugars, among other impacts. In type 2 diabetes it is thought that stress can exert an effect on blood glucose control, either directly through these hormones or indirectly by disruption of the diabetes self-care regimen. Although the laboratory and clinical research to date does not appear to support a consistent...

Transcutaneous electrical nerve stimulation TENS influences neuronal afferent transmission and conduction velocity, increases the nociceptive flexion reflex threshold, and changes the somatosensory-evoked potentials. In a 4-week study of TENS applied to the lower limbs, each for 30 min daily, pain relief was noted in 83 of the patients compared to 38 of a sham-treated group. In patients who only marginally responded to amitriptyline, pain reduction was significantly greater following TENS given...

The incidence of ESRD in diabetic patients has continued to increase despite the extensive use of ACEi to prevent DN. Recently, Suissa, et al. 75 have assessed the long-term effect of ACEi on the risk of ESRD in a population-based cohort of all diabetic patients treated with antihypertensive drugs between 1982 and 1986. The cohort of 6102 patients, in which 102 cases developed ESRD until 1997, were matched to 4129 controls. Relative to thiazide diuretic use, the adjusted rate ratio of ESRD...

The natural history can be divided into the following stages 9 1. Normal foot. The foot is normal and does not have the risk factors of ulceration namely neuropathy, ischemia, deformity, callus and edema. 2. At-risk foot. The patient has developed one or more risk factors noted in stage 1. 3. Foot with ulcer. There are two main types of diabetic foot, which have characteristic ulceration ulceration in the neuropathic foot develops at the sites of high mechanical pressure on the plantar surface....

Recently, several meta-analyses 66-69 comparing the effects of ACEi and ARB for preventing the development and progression of DN were published. Surprisingly, these reports reached totally different conclusions indicating the well known discrepancies between meta-analyses and subsequent large randomized, controlled trials 70 . In 2004, Strippoli GF, et al. 66 analyzed 43 trials with a total of 7545 patients 36 of 43 identified trials compared ACEi with placebo 4008 patients , 4 compared ARB...

Although free fatty acids FFA , also termed NEFA, acutely increase insulin secretion, chronic FFA overload diminishes beta-cell function. Type 2 diabetes subjects have often increased FFA due to insulin resistance to adipocytelipolysis. It is now clear that high glucose inhibits beta-cell fatty acid oxidation, which may lead to accumulation of long-chain FIGURE 6 Schematic representation of possible negative influences of hyperglycemia and increased NEFA, and of various modulators involved in...

AGIs have very few contraindications. They should not be given to patients with diverticulosis, large hernia, acute gastrointestinal diseases, colitis, inclusive and obstructive diseases of the bowel because of their adverse effects on gas production in the bowel, particularly in the colon. Pregnancy and lactation period are contraindications. For acarbose, but not for miglitol, severe renal insufficiency serum creatinine gt 3.5mg dL is a contraindication. Bile acid adsorbents, such as...

From a pathogenic viewpoint a number of different molecular mechanisms have been proposed for the development of the various manifestations of diabetic retinopathy. The underlying abnormalities may also play a role in the microvascular disease that results in nephropathy and possibly neuropathy. Many of these theories have been studied extensively in animals and humans using both in vitro and in vivo methods. The primary goal of these studies was to try and identify the underlying mechanisms...

In order to better understand whether severe insulin resistance can lead to frank diabetes, and to delineate the roles of the various insulin-sensitive tissues, the question has arisen whether it would be possible to induce diabetes in animal models harboring genetic defects leading to absence of insulin receptors in specific tissues brain, muscle, liver, adipocytes, and pancreas islets . Therefore, animal models with conditional knockouts of the insulin receptor have been studied Fig. 3 ....

In clinical practice one speaks of diabetic coma even if the patient has not lost conscious. About 10 of patients with coma diabeticum are really unconscious 6 . The causes of these conscious disturbances are cerebral dysfunction in association with severe hypertonic dehydration. The transition from hyperglycemic decompensation with severe ketoacidosis toward coma diabeticum is substantially dependent on the extent of the increase in serum osmolality. The consciousness correlates best with...

A severe, but avoidable complication of therapy is cerebral edema 9 . Brain edema is observed mostly 3 to 13 hours after beginning of therapy. It must be considered especially in patients below 20 years. In one study in children and young adults a total of 55 death cases were investigated 35 . Thirty-six of these patients had a ketoacidosis. A further retrospective study in children investigated searched for risk factors for the development symptomatic brain edema 33 . The prevalence of...

The therapy with bicarbonate is one of the mostly discussed procedures of management in the treatment of diabetic ketoacidosis. In general, acidosis is decreased after adequate rehydration and implementation of insulin treatment. The main indication for bicarbonate is the emergency treatment of serious disturbances of heart rhythm with severe acidosis and hyperkalemia. In such cases a body weight-adjusted amount of sodium bicarbonate e.g., 50-100 mL is infused. Otherwise, bicarbonate therapy...

An enormous amount of research has been dedicated to unraveling the pathophysiology of type 2 diabetes mellitus over the last 30 years. While a large number of reviews have been devoted to its description, this chapter follows the line of our recent seminar 1 . Insulin is the key hormone for regulating blood glucose. In general, normoglycemia is maintained by the balanced interplay between insulin secretion and the efficacy of insulin actions. In the fasting state, the major part of glucose is...

Diabetes mellitus type 2 is the most common endocrine-metabolic disorder and affects at least 5 of Western society. According to the persisting trends for increasing obesity, the amount of newly diagnosed patients will increase dramatically over the next decades. Unfortunately, lifestyle in combination with affluent alimentation does not spare the young, and increasing obesity in this group is already observed. Usually diabetes mellitus occurs at ages over 40 but we now observe a shift in the...

The clinical exam and Rose questionnaire are useful though unfortunately fairly insensitive tools for the diagnosis of lower extremity vascular disease 163 . Ancillary modalities include the ABI, toe systolic blood pressure, ultrasound duplex scanning, tissue PO2 measurement, and arteriography. The ABI is a ratio of Doppler recorded systolic arterial blood pressures in the lower and upper extremities, 166 and is normally between 1.00 and 1.40 167 . PAD is defined as an ABI less than 0.9. Lower...

Necrosis has very grave implications, threatening the loss of the limb and is caused by infection or ischemia or by both together. It is classified as either wet or dry, each with its specific management. In the neuropathic foot, necrosis is invariably wet initially and is nearly always due to a septic arteritis secondary to soft tissue infection complicating a digital or metatarsal ulcer. The arterial lumen is often occluded by a septic thrombus. Both wet and dry necrosis can occur in the...

Non-Proliferative Diabetic Retinopathy Management of NPDR relies heavily on patient education, periodic screening and, when necessary, laser treatment. The American College of Physicians American Academy of Ophthalmology has recommended a schedule for ophthalmic evaluation for patients with diabetes Table 1 . Periodic eye examinations enable ophthalmologists to identify patients who would benefit from prophylactic treatment, before serious complications develop. The potential sight-threatening...

The normal insulin need is about 1 IE hr and should be adapted to the increased needs depending on the extent of ketoacidosis, sepsis, overweight, activation of counter regulatory hormone systems and eventually therapy with catecholamines or glucocorticoids leading to insulin resistance. The guidelines of the German diabetes association recommend the low-dose insulin therapy with a starting dose of 6 IE hr 0.1 IE kg bodyweight until ketoacidosis is controlled and blood glucose is lowered to 14...

Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, U.S.A. Type 2 diabetes mellitus is defined by hyperglycemia, which is the result of an inability of the pancreas to make enough insulin for an individual's insulin resistance. Once this relative deficiency in insulin develops, the ability to produce insulin is no longer balanced with the insulin resistance and hepatic glucose production, thus the sugar...

The gold standard in the dietary treatment of obese patients with type 2 diabetes is a balanced moderately energy-restricted diet. The energy deficit is between 500 and 800 kcal day. The most important single measure is the reduction in fat intake, particularly in saturated fatty acids. It is generally recommended to prefer a high-carbohydrate low-fat diet. As shown TABLE 5 Obesity Prevention and Treatment Flowchart 18.5-24.9 Normal weight BMI 18.5-24.9 plus risk factors s and or comorbidity...

Department of Medicine, Cardiovascular Medicine Division, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, U.S.A Cardiovascular disease is a leading cause of death in the diabetic population, accounting for close to 80 of the mortality in diabetic patients in North America 1,2 . Patients with diabetes mellitus have both a significantly higher risk for, and a higher mortality from, coronary artery disease CAD . The diabetic patient has a two-to four-fold increase in the...

Intracavernosal therapy requires some specialist knowledge and the ability to treat priapism should it occur. Many specialists used to regard this as the standard treatment and use it for both diagnostic and therapeutic reasons although its role as first-line therapy has been replaced by less invasive treatment modalities. Patients need to be taught how to perform self-injection and the dose needs to be chosen carefully to avoid prolonged erections or priapism. Some patients find it helpful to...

The following basic diagnostic steps are needed usually during the first 24 hours clinical history, physical examination, clinical chemistry including TSH, parameters of sepsis, blood gases, urine status, blood and urine cultures in case of signs of infection, ECG, ultrasound of the abdomen, chest X-ray and eventually echocardiography. Especially in the beginning of the therapy of diabetic ketoacidosis, regular control of capillary blood glucose, potassium, and blood gases is needed. Initially,...

Features of diabetic retinopathy, including microaneurysms, cotton wool spots CWS , retinal edema, exudates, venous abnormalities and neovascularization, are all secondary to compromised capillary endothelium, which leads to increased capillary permeability and fragility. Widespread small vessel damage leads to areas of ischemia, which can promote intraocular angiogenesis. Numerous hypotheses explaining the microvascular complications of diabetes have been investigated, including the role of...

The glucose-lowering potential of guanides was first described in medieval times when extracts of Galega officinalis goat's rue or French lilac were used as treatment of diabetes in Europe 1 . In 1957, metformin, a dimethylated biguanide, and phenformin, a phenetylated biguanide were introduced for the therapy of type 2 diabetes mellitus Fig. 1 . Because of the strong association with lactic acidosis, phenformin was withdrawn in the 1970s in most countries including the United States 2 . In...

Endogenous GLP-1 concentrations can be raised two- to threefold by inhibiting GLP-1 degradation via DPP-4. Support for this approach to therapy also comes from the observations that glucose tolerance is improved in animals in which the enzyme has been genetically deleted 75 and in animals treated with DPP-4 inhibitors 76 . Various substances with DPP-4 inhibition properties are currently being tested in preclinical and clinical trials. The two compounds have reached approval in several...

Diabetes educators often find themselves faced with the challenge of starting a diabetes education program service or they are hired to manage one. For many educators with varying levels of clinical competence, starting, coordinating or managing a diabetes self-management program poses many challenges, and the development of additional skills for diabetes educators has become as important as clinical skills. These skills include Strategic and business planning Continuous quality improvement CQI...

Numerous peptide hormones play a role in the regulation of intestinal motility and gastric emptying and also directly, or indirectly, in the control of satiety and caloric intake. Some of these peptides are also involved in glycemic control. These hormones may also influence the neural control of gut motility. Glucagon-like peptide-1 GLP-1 arises from the differential post-transcriptional processing of the proglucagon gene that occurs in the intestinal L cells and in the hypothalamus. It is an...

Thiozolidindiones TZDs-Rosiglitazone and Piogitazone induce peripheral tissue sensitization to insulin by binding to nuclear peroxisome proliferators-activated receptor-y or PPAR-y, thus stimulating the transcription of genes that regulate carbohydrate and lipid metabolism. Studies have shown reduction of insulin resistance by up to 33 49 with the use of TZDs. Furthermore, recent data suggest that TZDs improve P-cell function by as much as 65 48 . Remarkable response to the metabolic effects of...

Type 2 diabetics unable to increase endogenous insulin secretion may behave metabolically in the perioperative period similar to the classic patient with type 1 diabetes 1,14,44 . Insulin therapy and frequent blood glucose monitoring are required to minimize the risk for ketoacidosis and hypoglycemia 16,17 . A variable-rate insulin infusion fixed-rate glucose infusion method provides the greatest flexibility, safety, and degree of glycemic control. Surgery should be scheduled as early in the...

The transition from i.v. insulin therapy to subcutaneous insulin and oral nutrition can be initiated in an awake patient when significant improvement and a pH-value of gt 7.2 have been reached. It is recommended to pursue a primary intensified therapy with pre-prandial applied doses of short acting insulin analogs combination with the prolonged acting insulin two or three times per day, or alternatively very long acting insulin analog once or twice a day. The first dose of long acting insulin...

The ethnic disparity observed in the rates of diabetic nephropathy, neuropathy and retinopathy disappears when the ethnic groups are maintained at a comparable level of glycemic control. Response to lifestyle or pharmacological intervention was also similar among the ethnic groups in the DPP study 46 . These findings raise hope and confidence that the high morbidity of diabetes in the ethnic minority groups can be ameliorated provided the barriers to the delivery of optimal care are identified...

Diabetic and non-diabetic patients develop hyperglycemia during surgery and medical illness due to enhanced hepatic gluconeogenesis, relative insulin deficiency, and decreased sensitivity of the liver, skeletal muscle, and adipose tissue to the actions of insulin 1-3 . While clinical evidence suggests a direct association between hyperglycemia and adverse outcome in patients undergoing vascular and cardiac surgery, there is little prospective data available to indicate that glucose control...

Classically, the treatment of osteomyelitis is surgical removal of bone. But long-term suppressive antibiotic therapy is also used. As osteomyelitis is usually associated with an infected ulcer and cellulitis, wide spectrum antibiotics should be initially given. On review, antibiotic selection is guided by the results of cultures. Ideally percutaneous bone biopsy should be carried out but this is not always practical especially in ischemic feet. Bone fragments in the base of the wound should be...

Division of Endocrinology, Diabetes, and Metabolism, University of Tennessee Health Science Center, Memphis, Tennessee, U.S.A. Diabetes mellitus is a chronic debilitating disease currently estimated to affect 7 over 20 million of the total population of the United States 1 . Type 2 diabetes accounts for 90 to 95 of all cases of diabetes. Studies show that the prevalence of diabetes is disproportionately higher among ethnic minority groups, including African Americans, Asian Americans, Pacific...

Dialysis catheter-type glucose sensors consist of a flexible catheter that the patient inserts through the skin into the sc tissue. The small pore dialysis catheter is connected to a fluidics system that transports a salt solution dialysate into and out of the body. Glucose-free dialysate is infused into the dialysis catheter previously inserted into the sc tissue, and allowed to equilibrate with ISF glucose. Glucose containing dialysate is pumped out of the body to an external electrochemical...

The glucose-lowering effect of metformin, monotherapy or in combination, has been extensively reviewed 70-72 . In a meta-analysis 73 all randomized, controlled clinical trials comparing metformin with placebo 29,62,74-80 and sulfonylurea 62,74,81-87 were evaluated. The weighted mean difference between metformin and placebo after treatment median treatment duration 4.5 months for fasting blood glucose was -2.0 mM and for HbA1c -0.9 . Body weight was not significantly changed after treatment....

Islet cell autoantibody testing is not always reliable, and the results are not immediately available. Thus, the physician must depend on clinical judgment in classifying new-onset diabetes patients. The pathways in bold in the decision trees provided in Figure 1 indicate the most likely outcomes. Classification may only be possible after months or longer of follow-up. In African American children with new, acute-onset diabetes, islet autoantibody testing can identify many of the children who...

The safety and efficacy of continuous peritoneal insulin infusion CPII therapy using a programmable implantable insulin pump have been demonstrated in patients with type 1 and type 2 diabetes. An external programmer is used to control the basal rate and timing amount of a regular insulin bolus infused prior to meals. Peritoneal insulin delivery significantly reduces the risk of hypoglycemia, an advantage that may be due to portal delivery of insulin and a more physiological ratio of portal to...

The criteria in clinical chemistry of a diabetic coma are summarized in Table 2 8 approximately 15 of patients with diabetic ketoacidosis have glucose concentration in plasma lt 350mg dL. In these cases one speaks of euglycemic diabetic ketoacidosis. This appears in situations in which gluconeogenesis appears to be disturbed, e.g., liver disease, alcoholism, prolonged fasting or in cases where insulin-independent glucose consumption is very high i.e., in pregnancy . In cases where blood glucose...

Early in the first half of the 20th century it was already hypothesized that gastrointestinal hormones are important for glucose homeostasis and stimulation of insulin secretion after a meal 1,2 . In the late 1960s it was finally shown that orally administered glucose leads to a greater insulin response than intravenously administered glucose dosed to lead to identical serum glucose excursions 3 . This difference in insulin secretion is termed the incretin effect. The gastrointestinal hormones...

The epidemic of obesity, and the difficulty in losing accumulated weight suggest that there may have been an advantage to this metabolic phenotype during human evolution. The development of type 2 diabetes in susceptible individuals would not have been a disadvantage in the absence of opportunities to become obese. The thrifty genotype hypothesis was first advanced by JV Neel 24 nearly 40 years ago and recently updated 32,33 . This hypothesis explains the insulin resistance and relative beta...

Patients use the real-time glucose trend data displayed on the hand-held CGM monitor to make more appropriate clinical decisions regarding BG control 20,22,23 . The Food and Drug Administration FDA , however, does not currently allow the patient with diabetes to initiate a change in medical therapy insulin or oral hypoglycemia medication based solely upon CGM glucose sensor data. Diabetic patient are therefore required to adjust drug therapy according to traditional SMBG measurements. This...

Thiazides have been associated with glycemic disturbance for many decades. In 1981, a randomized, controlled trial from the Medical Research Council suggested that patients receiving bendrofluazide developed more impaired glucose tolerance IGT than those receiving propranolol 15.4 vs. 4.8 cases patient-years, respectively 13 . This study was criticized for using extremely high dose of bendrofluazide. There are, however, many prospective clinical trials that have demonstrated definite adverse...

In the context of two major physiologic defects, insulin resistance and insulin secretory failure, combination treatments with differing actions are entirely logical. Several different advantages of combining agents can be distinguished. The first rationale for combination therapy either with oral agents alone or with oral agents and insulin or oral agents with other injectable medicine such as incretin mimetics is its superior efficacy. One principle that emerges from randomized controlled...

The evaluation of upper GI symptoms in patients with diabetes by means of esophagogas-troduodenoscopy may document the presence of intercurrent conditions such as peptic ulceration, peptic stricture or Mallory-Weiss tears a result of repeated retching and vomiting . The presence of bezoars suggests delayed gastric emptying. Confirmation of the diagnosis of gastroparesis requires documentation of delayed gastric emptying. Scintigraphic transit studies are typically used to measure gastric...

Animas Corporation is developing a long-term implantable sensor that uses near-infrared spectroscopy to measure the concentration of glucose in blood. The system resembles a pacemaker with an sc electronics optical module and a miniature sensor head that is surgically implanted around a blood vessel. A universal calibration algorithm has been developed that allows glucose to be accurately predicted from the optical spectra. The system has been designed to overcome the biocompatibility...

The development of the glycosylated hemoglobin assay has become one of the major advances in taking care of patients with diabetes mellitus. The glycohemoglobin measurement correlates with fasting blood glucose, postprandial glucose, the glucose peak during an oral glucose tolerance test and the mean glucose levels over many weeks. Currently most laboratories use the HbA1c measurement but this is not universal. After the results of the DCCT were published the use of the HbA1c level in setting a...

The etiology of PCOS, most likely a combination of genetic disposition and environmental factors, is not completely understood 23,24 . While familial clustering of PCOS has been well documented, even including a male factor with higher androgen levels in first degree relatives of affected patients 25,26 , the search for candidate genes has not come up with obvious culprits 27,28 . While not its cause, insulin resistance plays a pathogenic role in the development of PCOS. Hyperinsulinemia...

The implantable tissue fluid glucose sensor developed by DexCom Corporation has been tested long-term in ambulatory patients with type 1 diabetes http www.DexCom.com . Patients successfully used the real-time glucose sensor data to improve fasting and postprandial glucose control while virtually eliminating hypoglycemia. A surgeon can easily implant the miniature sensor within the sc tissue of the abdomen or chest wall. The sensor contains the enzyme glucose oxidase and electrodes covered by a...

For almost 40 years of research, the precise cellular mechanism of metformin action has been a mystery. While depending on the researcher's background, the experimental system used or the available assay, a great many cellular mechanisms have been described but a single unifying site of action such as a receptor, an enzyme, or a transcription factor, had stubbornly escaped detection. Throughout this quest it was generally undisputed that metformin had no effect on the pancreatic beta cell in...

Multiple mechanisms have been postulated to explain drug-induced diabetes 6 . Some of these mechanisms have been confirmed while others are conflicting. It is important to remember that a drug can act through more than one mechanism. In general, these mechanisms can be classified into four categories effects on insulin release, effects on insulin sensitivity, effects on liver, and effects on peripheral blood flow Figure 1 . i. Inhibition of insulin release will result in hyperglycemia, and...

Sulfonylureas cause a moderate improvement in the lipid profile due to improvement of lipid metabolism by increased levels of insulin and lowered level of glucose, which is considered an indirect effect. Large randomized trials, such as the UKPDS, usually showed a weight gain of 2 to 4 kg with longer acting sulfonylureas, e.g., glibenclamide and chlorpropamide. This weight gain can be avoided by dietary advice if patients are compliant. Indeed, no weight gain was observed in smaller studies...

In diabetic ketoacidosis, very frequently severe hyperventilation with deep respiratory breaths are observed, also called Kussmaul-respiration. This is a compensatory mechanism aiming to get rid of CO2 in cases of severe metabolic acidosis. The blood gases show severely lowered pCO2, a relatively high pO2 with relatively high hemoglobin O2 saturation as well as low standard bicarbonate. Respiratory compensation by hyperventilation is a compensatory mechanism this is the reason why medications...

It is thought that by eliminating the discomfort of finger-stick sampling, patients would SMBG more frequently. To be clinically useful, non-invasive glucose monitoring systems would have to be small, light weight, portable, safe and accurate. A variety of optical methods have been devised to measure glucose in blood, interstitial fluid ISF and eye fluid 15,16 . The prototype devices require sophisticated optics and electronics for stability and high signal-to-noise. Unfortunately, there...

FIGURE 1 Control of gastrointestinal motility. Note the extrinsic or autonomic nervous system modulates the function of the enteric nervous system, which controls smooth muscle cells through transmitters. Source From Ref. 72. gastroparesis and only 0.6 had nocturnal diarrhea. This discrepancy has been addressed in other community-based epidemiological studies, which are discussed below. Kassender recognized asymptomatic gastric retention in diabetics in 1958 7 and coined the term gastroparesis...

Treatment goals for diabetes demand near-normal glucose levels if possible in view of patient compliance and ability to follow therapeutic recommendations. This should be achieved with diet and exercise whenever possible. In the early phase of type 2 diabetes, insulin secretion typically is elevated 8 , compared with healthy subjects, in an attempt to compensate for insulin resistance. Nevertheless, the chronically elevated levels of glucose, as occurs in manifest type 2 diabetes, indicate...

While general autonomic reflex tests 62 are useful to assess the function of the autonomic control of the viscera Table 3 , tests that are specific for gut autonomic innervation are A Pancreatic polypeptide response to hypoglycemia or to modified sham feeding by the chew and spit technique Pancreatic polypeptide concentrations rise after meal ingestion and delivery of nutrients to the duodenum 63 . Atropine or vagotomy abolish this response. Normally, pancreatic polypeptide concentrations...

Patients with severe exacerbation of symptoms should be hospitalized and may require nasogastric suction. Intravenous fluids should be provided, and metabolic derangements ketoacidosis, uremia, hypo hyperglycemia corrected. Parenteral nutrition may become necessary in cases of malnutrition. Bezoars may be mechanically disrupted during endoscopy, followed by gastric decompression to drain residual nondigestible particles. Erythromycin at a dose of 3 mg kg body weight intravenously every 8 h...

Surgical patients are typically converted from an intravenous infusion of insulin to intermediate injections of insulin once tolerating a liquid diet. The morning dose of basal insulin NPH or Glargine and prandial insulin Regular or Lispro are injected prior to breakfast, according to the amount of insulin delivered over the prior 24-h, the anticipated carbohydrate composition of the meal, and the fasting BG measurement. The IV infusion of regular insulin is typically discontinued 60min after...

Among sulfonylureas, no definitive advantages have been demonstrated for one compound compared with others in trials with hard endpoints. The potent long-acting sulfonylureas bear a higher risk of protracted hypoglycemias in elderly people who may miss meals, and in poorly controlled conditions. Shorter acting and less potent insulin releasers may be advantageous under these circumstances 16,28 . Specific advantages have been proposed for gliclazide, due to its antioxidant actions, and...

The GI symptoms that are frequently encountered in patients with diabetes mellitus are outlined in Figure 2. Diabetic enteropathy refers to all the GI complications of diabetes and may result in dysphagia, heartburn, nausea and vomiting, abdominal pain, constipation, diarrhea and fecal incontinence 3 . Feldman and Schiller reported that 76 of referrals to a diabetic clinic had at least one GI symptom 3 . Clouse also reported that GI symptoms were present in a high proportion 20 of diabetic...

Subcutaneous tissue injection continues to be the most common route for insulin delivery in the pre and post-operative period. Absorption of regular insulin from the subcutaneous tissue is often slow and variable. The coefficient of variation between patients has been shown to exceed 50 and intra-individual coefficient of variation exceeds 25 45 . Greater variability of absorption should be expected in the hospitalized patient. Sliding-scale insulin regimens based upon retrospective...

A variable-rate intravenous infusion of regular insulin is the safest and most versatile way to manage blood glucose levels during and after major surgery Table 2 . The safety of an intravenous infusion regimen has been demonstrated in the operating room, intensive care unit, and general surgical floor 2,9,11,42 . The usual starting dose for a variable-rate insulin infusion is 1.0 U h, with smaller starting doses recommended in patients with high insulin sensitivity athletes and thin women ....

An alternative intravenous insulin regimen contains a fixed concentration of glucose, potassium, and regular insulin in one solution bag. The GIK regimen gained widespread clinical acceptance in the 1970s because of its simplicity and safety. Insulin and glucose are delivered in balanced proportions at a constant rate 100ml h without the need for an electronic pump. Unfortunately, this method lacks flexibility and often fails to achieve desired glucose control, compared to the variable-rate...

Thiazolidenediones TZD , including pioglitazone and rosiglitazone, work by enhancing insulin-mediated glucose uptake however, their effects are pleiotropic and their mechanisms of action are incompletely understood. Weight gain 5 to 10 kg is common with TZD therapy. Fluid retention and edema formation can occur and TZD may precipitate clinical deterioration in patients with congestive heart failure. This adverse effect appears to occur more frequently when TZD are used in combination with...

The bolus intravenous injection of regular insulin is the most common method used by anesthesiologists to control blood glucose levels 44,46,47 . This method is without physiological basis and cannot be recommended. The short pharmacokinetic 4-7 min and TABLE 3 Variable-Rate Insulin Infusion Regimen for Tight Blood Glucose Control Fixed-Rate Glucose Infusion TABLE 3 Variable-Rate Insulin Infusion Regimen for Tight Blood Glucose Control Fixed-Rate Glucose Infusion